Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat

Research suggests that use and abuse of marijuana can be especially harmful if it occurs during adolescence, a period of vast developmental changes throughout the brain. We examined the effects of 2mg/kg (9)-tetrahydrocannabinol (THC) administered daily via intra-peritoneal injections during juvenile/early adolescence (postnatal day 22-40) or late adolescence (postnatal day 41-60) on locomotor activity, development of tolerance, and acquisition/retention of spatial avoidance in adulthood. THC caused locomotor depression in both male and female animals dosed during early adolescence but only in female animals dosed during late adolescence. Evidence of reverse tolerance to THC was seen in early adolescent animals only. In the active place avoidance test (APA), male and female animals administered THC during early adolescence made more errors on the reversal trial requiring flexibility in learning, but in animals dosed during late adolescence there were no significant sex or treatment differences. The results of the locomotor activity study indicate that females may be more sensitive to the effects of THC than males, while results of both locomotor activity and APA studies suggest that early adolescents appear to be more vulnerable to these effects than late adolescents/young adults.